Functional Hydrogels Promote Vegetable Growth in Cadmium-Contaminated Soil.

Over the years, the concentration of cadmium in soil has increased due to industrialization. Cadmium in the soil enters the human body through plant accumulation, seriously endangering human health. In the current study, two types of hydrogels were successfully synthesized using a free radical polymerization method: an ion-type hydrogel referred to as DMAPAA (N-(3-(Dimethyl amino) propyl) acrylamide)/DMAPAAQ (N,N-Dimethyl amino propyl acrylamide, methyl chloride quaternary) and a non-ion-type hydrogel known as DMAA (N,N-Dimethylacrylamide). In the experiment carried out in this study, the ion-type hydrogel DMAPAA/DMAPAAQ was introduced to cadmium-contaminated soil for vegetable cultivation. The study found that at cadmium levels of 0 and 2 mg/kg in soil, when exposed to a pH 2 solution, cadmium wasn't detected in the filtrate using ICP. As the amount of cadmium increased to 500 mg/kg, hydrogel addition gradually reduced the filtrate cadmium concentration. Notably, the use of the 4% hydrogel resulted in 0 mg/L of cadmium. For the 0% hydrogel, vegetable cadmium absorption was determined to be 0.07 mg/g, contrasting with 0.03 mg/g for the 4% hydrogel. The DMAPAA/DMAPAAQ hydrogel significantly boosts vegetable growth by efficiently absorbing nitrate ions through ion exchange, releasing them for plant uptake. In contrast, the DMAA hydrogel, used as a control, does not enhance plant growth despite its water absorption properties. In summary, the composite hydrogel shows great potential for enhancing vegetable yield and immobilizing heavy metals in soil.

Tooth morphology fusion technique is more accurate than conventional technique in transferring morphology of provisional to definitive screw-retained, implant-supported crown: A preliminary intervention study.

PURPOSE: To compare the accuracy of the tooth morphology fusion (TMF) digital technique and customized impression transfer coping (conventional) technique when transferring the morphology of a provisional crown to a definitive screw-retained implant-supported crown. METHODS: Six cases of partial edentulism (one anterior and five posterior) treated with oral implant placement in our clinic for the loss of three or fewer teeth in the maxilla or mandible between April 2017 and September 2018 were included. After implant placement and re-entry surgery, provisional restorations were made and adjusted to obtain the ideal morphology. Two definitive restorations were constructed by transferring the complete morphology of the provisional restorations, including the subgingival contour, using the TMF digital and conventional techniques. Three sets of surface morphological data were obtained using a desktop scanner. The three-dimensional total discrepancy volume (TDV) between the provisional restoration (reference) and the two definitive restorations was digitally measured by overlapping the surface data of the stone cast using the Boolean operation. Each TDV ratio (%) was calculated by dividing the TDV by the volume of provisional restoration. The median TDV ratios for TMF and conventional techniques were compared using the Wilcoxon signed-rank test. RESULTS: The median TDV ratio between provisional and definitive restorations constructed using the TMF digital technique (8.05%) was significantly lower than that obtained using the conventional technique (13.56%, P < 0.05). CONCLUSIONS: In this preliminary intervention study, the TMF digital technique was more accurate than the conventional technique for the transfer of morphology from provisional to definitive prosthesis.

Dual Benefits of Hydrogel Remediation of Cadmium-Contaminated Water or Soil and Promotion of Vegetable Growth under Cadmium Stress.

This study aims to solve the problem of cadmium heavy metal ion pollution caused by the abuse of chemical fertilizers and activities such as mining, which pose a serious threat to the plant growth environment. We successfully synthesized DMAPAA (N-(3-(Dimethyl amino) propyl) acrylamide)/DMAPAAQ (N, N-Dimethyl amino propyl acrylamide, methyl chloride quaternary) hydrogels via free radical polymerization. Subsequently, we conducted experiments on this hydrogel for growing vegetables under cadmium stress conditions in aqueous solutions and soil. The cadmium capture capacity of DMAPAA/DMAPAAQ hydrogels under different cadmium ion concentrations and pH values was evaluated by using inductively coupled plasma optical emission spectrometry (ICP). The research results show that under the condition of pH = 7.3, the cadmium capture capacity of DMAPAA/DMAPAAQ hydrogels is the greatest. We used the Langmuir model to fit the adsorption data, and the correlation coefficient was as high as 0.96, indicating that the model fits well. The application of the hydrogels promoted the growth of vegetables in soil under cadmium stress conditions. The results showed that when the added amount of hydrogel was 4%, the dry weight of the vegetables was the largest. In addition, when the added amount of cadmium was 500 mg/kg and the added amount of hydrogel was 4%, the absorption of cadmium by the vegetables decreased to an undetectable level. In summary, the hydrogel successfully synthesized in this study can be effectively used to immobilize cadmium ions in soil while positively promoting the growth and yield of vegetables. This achievement has practical significance for solving the problem of heavy metal ion pollution.

[A case of fascioliasis].

A 38-year-old rice farmer visited a hospital for abdominal pain. Computed tomography (CT) showed a liver tumor and magnetic resonance imaging (MRI) revealed a hypovascular tumor, both in segment 4. Thus, he was diagnosed with liver abscess. Ten days later, CT showed a new liver tumor in segment 8, but the size of the liver tumor in segment 4 had decreased. He was suspected with parasitic disease because of eosinophilia. Enzyme-linked immunosorbent assay showed a high level of serum Fasciola antibody. The patient was diagnosed with fascioliasis and was treated with triclabendazole. Post-treatment, CT revealed that the liver tumors had shrunk. Eosinophilia and multiple lesions were characteristic findings of parasitic disease.

Enzymatic properties and clinical associations of serum alpha-galactosidase A in Parkinson's disease.

OBJECTIVE: Recent studies have revealed an association between Parkinson's disease (PD) and Fabry disease, a lysosomal storage disorder; however, the underlying mechanisms remain to be elucidated. This study aimed to investigate the enzymatic properties of serum alpha-galactosidase A (GLA) and compared them with the clinical parameters of PD. METHODS: The study participants consisted of 66 sporadic PD patients and 52 controls. We measured serum GLA activity and calculated the apparent Michaelis constant (Km ) and maximal velocity (Vmax ) by Lineweaver-Burk plot analysis. Serum GLA protein concentration was measured by enzyme-linked immunosorbent assay. We examined the potential correlations between serum GLA activity and GLA protein concentration and clinical features and the plasma neurofilament light chain (NfL) level. RESULTS: Compared to controls, PD patients showed significantly lower serum GLA activity (P < 0.0001) and apparent Vmax (P = 0.0131), but no change in the apparent Km value. Serum GLA protein concentration was lower in the PD group (P = 0.0168) and was positively associated with GLA activity. Serum GLA activity and GLA protein concentration in the PD group showed a negative correlation with age. Additionally, serum GLA activity was negatively correlated with the motor severity score and the level of plasma NfL, and was positively correlated with the score of frontal assessment battery. INTERPRETATION: This study highlights that the lower serum GLA activity in PD is the result of a quantitative decrement of GLA protein in the serum and that it may serve as a biomarker of disease severity.

What can surgeons do to prevent job leave soon after cancer diagnosis? A brief report on colorectal cancer survivors in Japan.

PURPOSE: Colorectal cancer is one of the most diagnosed cancers in Japan and the number of cancer survivors has increased. Work-related issues of cancer survivors have been investigated in relation to occupational health, and sufficient evidence in clinical practice is needed to support this. This study aimed to obtain the relevant information, intending to support the employment of patients with colorectal cancer for clinical settings. METHODS: We conducted a prospective, multicenter cohort study, which included patients who underwent surgery with clinical stage I-III colorectal cancer. An electronic survey was used at the time of hospital admission to collect the patients' occupational information, including job resignation soon after cancer diagnosis. A cross-sectional analysis was performed to evaluate the patients' employment situations. RESULTS: Of 129 eligible patients, 46 (36%) were female. Thirty-nine (30%) were self-employed and 72 (56%) worked at small-sized workplaces, which are not obliged to have occupational physicians. Most patients (89%) expressed their desire to return to work, but eight patients (6%) left their jobs soon after being diagnosed with colorectal cancer before undergoing surgery for several reasons stemming from worries about future treatment and its consequences. Multivariable analyses indicated that nonregular employees and the self-employed might be at a disadvantage in keeping their job at diagnosis. CONCLUSION: Surgeons should address work-related issues for survivorship, which begins at cancer diagnosis and, when available, collaborate with occupational physicians while being mindful that patients working at smaller companies do not have immediate access to occupational physicians.

Clinical Characteristics of Retroviral Rebound Syndrome: A Case Report and Literature Review.

We herein report a case of retroviral rebound syndrome (RRS) complicated with hemophagocytic lymphohistiocytosis. Owing to the paucity of comprehensive data on RRS, we also conducted a literature review. All 19 cases included in the review presented within 2 months after the discontinuation of antiretroviral therapy. They were usually accompanied by both a significant decrease in CD4 count (median 292/µL) and a rapid increase in plasma human immunodeficiency virus loads (median 3.5×105/mL). Although life-threatening complications were reported, the overall prognosis was favorable. The outcomes of this review aided in the diagnosis of the present case.

Factors Contributing to the Prognosis after Second-line Therapy with Ramucirumab in Advanced Hepatocellular Carcinoma.

Objective Multiple therapeutic agents exist for advanced hepatocellular carcinoma (HCC), but prognostic factors in second-line and subsequent therapies are unclear. Ramucirumab is a molecular-targeted agent effective against hepatocytes with alpha-fetoprotein (AFP) >400 ng/mL after sorafenib failure. We examined the prognostic factors and efficacy of ramucirumab with prior therapy other than sorafenib. Methods In our retrospective multicenter study, 33 patients were treated with ramucirumab for HCC with prior therapy other than sorafenib, including 1 patient who received 2 lines of ramucirumab. We analyzed background factors, liver reserve, the prognosis, and treatment duration and efficacy. Results The median albumin-bilirubin (ALBI) value showed little change during ramucirumab treatment. The ALBI value improved in 32% of patients, and their prognoses were better than in those who did not improve. Response and efficacy rates were not as high as those in the REACH-2 study but were similar when limited to patients with 2,500 ng/mL AFP. Thirteen patients received further treatment after ramucirumab failure and they had a significantly better prognosis from ramucirumab administration and also had a significantly better prognosis from the start of the first tyrosine kinase inhibitor than who did not received further treatment. In univariate and multivariate analyses of prognostic factors, the continuation of treatment with another drug after ramucirumab failure and a good ALBI value at initiation were significant. The presence of a ramucirumab response and treatment duration were not associated with the prognosis. A good ALBI value at initiation and ALBI value improvement during treatment were also identified as independent factors associated with eligibility for further treatment after ramucirumab failure. The treatment line did not correlate with the availability of treatment with another drug after treatment failure. Conclusions ALBI value improvement with ramucirumab treatment allows for subsequent treatment after failure and an improved overall prognosis.

Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma progressing after molecular targeted therapy: A multicenter prospective observational study.

To evaluate the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma (HCC) previously treated with molecular targeted agents (MTAs). Thirty-one patients treated with atezolizumab plus bevacizumab for unresectable HCC and previously treated with MTAs were enrolled in this study. The treatment lines ranged from second to sixth lines. The treatment effect on HCC differed from that during first-line treatment. The treatment effect was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST. The treatment response was different for each MTA immediately prior to atezolizumab + bevacizumab treatment. Tumors treated with lenvatinib followed by atezolizumab + bevacizumab showed rapid growth for a short period of time followed by shrinkage. However, patients who received ramucirumab, sorafenib, and regorafenib did not show such changes. This was likely because of differences in the mechanism of action of the MTA administered immediately beforehand. The side-effect profile differed from that observed in the IMbrave150 phase 3 study of atezolizumab plus bevacizumab, which showed more adverse events related to hepatic reserve. Patients treated with the combination of atezolizumab and bevacizumab after lenvatinib therapy may experience rapid tumor growth and subsequent shrinkage.

Detection of human herpesviruses in cerebrospinal fluids collected from patients suspected of neuroinfectious diseases.

The full spectrum of human herpesviruses (HHV)-associated neuroinfectious diseases in immunocompetent adults remains unclear. Hence, we sought to elucidate the epidemiology and clinical features of these diseases. The study subjects were patients over 16 years old suspected of neuroinfectious diseases who underwent spinal tap performed by neurologists in our university hospital between April 2013 and March 2018. The presence of seven HHV DNAs in cerebrospinal fluid (CSF) was determined by real-time PCR. HHV DNAs were detected in 33 (10.2%) of the 322 patients. The most frequently detected herpesvirus was varicella zoster virus (VZV) (19 patients), followed by HHV-6 (four patients), herpes simplex virus (HSV)-1 (three patients), HSV-2 (three patients), and Epstein-Barr virus (two patients). HHV DNAs were detected in CSF collected from patients with various neuroinfectious diseases, including myelitis, peripheral neuritis, encephalitis, and meningitis. All patients with HSV-1 DNA had encephalitis, whereas all patients with HSV-2 DNA had meningitis. Eleven of the 19 patients with VZV DNA had meningitis. Patients with VZV-associated encephalitis (median age, 80 years) were significantly older than non-encephalitis patients (median age, 60.5 years) (P = 0.046). Although post-herpetic neuralgia was observed in seven (54%) of the 13 patients with VZV and without encephalitis, no such neurological sequela was observed in the four encephalitis patients. In conclusion, HHVs were associated with approximately 10% of neuroinfectious diseases in this cohort. VZV was the most common pathogen, probably due to the large number of VZV meningitis patients. In addition, patients with VZV-associated meningitis were significantly younger than patients with VZV-associated encephalitis.

SARS-CoV-2-related Progressive Brain White Matter Lesion Associated with an Increased Cerebrospinal Fluid Level of IL-6.

We herein report a 49-year-old man with a fever, diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After two weeks of hospitalization, he suddenly mentioned visual field impairment. Computed tomography and magnetic resonance imaging revealed white matter damage and vasogenic edema. Cerebrospinal fluid showed increased levels of interleukin (IL)-6. His symptoms and white matter lesion deteriorated. After treatment with intravenous methylprednisolone therapy and plasmapheresis, his symptoms and white matter lesion improved gradually. We suspect that our patient was affected by a secondary hyperinflammatory syndrome related to cytokines, alone or in combination with direct viral injury through endothelial cell damage. The IL-6 levels were elevated only in the cerebrospinal fluid, suggesting focal central nervous system inflammation.

Partial reduced Pi transport function of PiT-2 might not be sufficient to induce brain calcification of idiopathic basal ganglia calcification.

Idiopathic basal ganglia calcification (IBGC) is a rare intractable disease characterized by abnormal mineral deposits, including mostly calcium in the basal ganglia, thalamus, and cerebellum. SLC20A2 is encoding the phosphate transporter PiT-2 and was identified in 2012 as the causative gene of familial IBGC. In this study, we investigated functionally two novel SLC20A2 variants (c.680C > T, c.1487G > A) and two SLC20A2 variants (c.82G > A, c.358G > C) previously reported from patients with IBGC. We evaluated the function of variant PiT-2 using stable cell lines. While inorganic phosphate (Pi) transport activity was abolished in the cells with c.82G > A, c.358G > C, and c.1487G > A variants, activity was maintained at 27.8% of the reference level in cells with the c.680C > T variant. Surprisingly, the c.680C > T variant had been discovered by chance in healthy members of an IBGC family, suggesting that partial preservation of Pi transport activity may avoid the onset of IBGC. In addition, we confirmed that PiT-2 variants could be translocated into the cell membrane to the same extent as PiT-2 wild type. In conclusion, we investigated the PiT-2 dysfunction of four SLC20A2 variants and suggested that a partial reduced Pi transport function of PiT-2 might not be sufficient to induce brain calcification of IBGC.

Changes in Serial D-Dimer Levels Predict the Prognoses of Trousseau's Syndrome Patients.

Background: The development of acute multiple embolic infarctions (AMEI) resulting from cancer is known as Trousseau's syndrome (TS). At present, however, there is no good marker for predicting the prognosis of TS patients. In the present study, we evaluated the use of serial D-dimer levels as a prognostic marker for TS. Methods: This retrospective cohort study included 1,409 consecutive acute ischemic stroke patients. We selected a group of patients with TS showing AMEI (n = 38; TS group) and a group of patients with atrial fibrillation (Af) and AMEI (n = 35; Af group) as controls. Serial D-dimer levels were measured between days 7 and 28 after stroke (sub-acute phase) in 21 patients of the TS group and 24 patients of the Af group. Results: D-dimer levels at onset (acute phase) were significantly higher in the TS group (8.45 ± 1.79 µg/mL, n = 38) compared with the Af group (1.14 ± 0.14 µg/mL, n = 35) (p < 0.0001). In patients for whom serial D-dimer measurements were made, D-dimer levels measured at the sub-acute phase decreased to 0.48 ± 0.12 µg/mL (n = 24) in the Af group, but remained elevated in the TS group during the sub-acute phase (11.20 ± 2.77 µg/mL, n = 21) (p < 0.0001). In all TS patients in whom serial D-dimer measurements were made, D-dimer levels in 17 patients who died within 500 days (13.31 ± 3.23 µg/mL) were significantly higher than those of the four surviving patients (2.23 ± 0.38 µg/mL) (cut-off D-dimer level = 3.0 µg/mL) during this period. Moreover, serial D-dimer levels of 10 patients who died within 90 days (17.78 ± 4.60 µg/mL) were significantly higher than those of the 11 patients who survived up to 90 days (5.21 ± 2.12 µg/mL) (p < 0.05). Conclusions: Serial D-dimer levels may be a good biomarker for TS as well as a useful predictor of the prognosis of TS patients.

Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity.

Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells. We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity. The data we present here strongly suggest that anti-GM1 caused a significant change in sphingomyelin content of the membrane fraction in PCtrk cells. Both nSMase2 activity and the level of nSMase2 protein were significantly decreased by anti-GM1 treatment of PCtrk cells, while acidic SMase activities remained unchanged. Our results indicate, for the first time, that anti-GM1 may produce profound impacts on lipid metabolism in neuronal cell membranes.

Differentiation of cancer from atrial fibrillation in patients with acute multifocal stroke.

OBJECTIVE: Acute multifocal embolic infarction (AMEI) is conventionally caused by etiologies such as cardioembolism due to atrial fibrillation (Af), but can also be caused by serious underlying diseases such as cancer. We characterized cancer-related AMEI and identified useful indicators for cancer-associated strokes. METHODS: A retrospective analysis was performed on 35 patients with Af-related AMEI and 35 patients with cancer-related AMEI selected from 1235 consecutive patients with acute infarcts. All patients received diffusion-weighted magnetic resonance (MR) imaging. Cerebral MR angiography, carotid and cardiac ultrasonography, electrocardiogram-monitoring and whole body computed tomography were also performed on these patients. D-dimer levels were evaluated on admission, and were measured during the sub-acute phase in 19 of the patients with Af and 27 of the patients with cancer. RESULTS: Acute phase D-dimer levels were significantly higher in patients with cancer than in patients with Af alone. The cut-off D-dimer value to identify cancer-associated infarcts was 2.0µg/mL. D-dimer levels during the sub-acute phase remained elevated in the cancer patients. CONCLUSIONS: We may differentiate cancer-associated AMEI from Af using a D-dimer level≥2.0µg/mL, which does not decrease during the sub-acute phase.

Histone deacetylase inhibitor attenuates neurotoxicity of clioquinol in PC12 cells.

Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore the further mechanism of neuronal damage by clioquinol, we evaluated the acetylation status of histones in PC12 cells. Clioquinol reduced the level of histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A upregulated acetylated histones and prevented the neuronal cell damage caused by clioquinol. In addition, treatment with HDAC inhibitor decreased neurite retraction and restored the inhibition of NGF-induced Trk autophosphorylation by clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol. Clioquinol is now used as a potential medicine for malignancies and neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate medicine for the prevention of its side effects on neuronal cells.

Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells.

Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin(®)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction.

Morphological changes of the hair roots in alopecia areata: a scanning electron microscopic study.

Alopecia areata is a chronic inflammatory condition causing non-scarring patchy hair loss. Diagnosis of alopecia areata is made by clinical observations, hair pluck test and dermoscopic signs. However, because differentiation from other alopecia diseases is occasionally difficult, an invasive diagnostic method using a punch biopsy is performed. In this study, to develop a reliable, less invasive diagnostic method for alopecia areata, we performed scanning electron microscopy of the hair roots of alopecia areata patients. This study identified four patterns of hair morphology specific to alopecia areata: (I) long tapering structure with no accumulation of scales; (II) club-shaped hair root with fine scales; (III) proximal accumulation of scales; and (IV) sharp tapering of the proximal end of hair. On the basis of these results, we can distinguish alopecia areata by scanning electron microscopic observation of the proximal end of the hair shafts.

Comparative study for the effect of photodynamic therapy, imiquimod immunotherapy and combination of both therapies on 40 lesions of actinic keratosis in Japanese patients.

We treated 12, 15 and 13 Japanese actinic keratosis (AK) lesions with 5-aminolevulinic acid photodynamic therapy (PDT), 5% imiquimod cream and combination of both therapies, respectively, and compared the effects. Patients underwent the second course, when AK lesions remained after the first course. Efficacy was evaluated 1 month after each treatment. Combination therapy cleared all AK lesions only after the first course, while PDT and imiquimod therapy cleared 41.7% and 66.7% of AK lesions after the first course, respectively. All residual AK lesions after the first course were cleared by the second courses of PDT or imiquimod therapy. During the course, erosion and crust developed significantly more frequently in combination therapy (P < 0.001). Most Japanese AK lesions can be satisfactorily treated with either PDT or imiquimod monotherapy. However, only severe cases may better be treated with combination therapy, which show higher efficacy even though adverse events occur frequently.